The impact of serum magnesium and calcium on the risk of epilepsy: A mendelian randomization study

Abstract

AimsTo investigate the causal role of serum magnesium and calcium in epilepsy or any of its subtypes through Mendelian randomization (MR) approach.MethodsSingle nucleotide polymorphisms (SNPs) associated with serum magnesium and calcium were used as the instrumental variables. MR analyses were performed using the summary‐level data for epilepsy extracted from International League Against Epilepsy Consortium (15,212 cases and 29,677 controls) to obtain the causal estimates. The analyses were replicated using FinnGen data (7224 epilepsy cases and 208,845 controls), and a meta‐analysis was then conducted.ResultsThe result of combined analyses showed that higher serum magnesium concentrations was associated with a reduced risk of overall epilepsy (odds ratios [OR] = 0.28, 95% confidence interval [CI], 0.12–0.62, p = 0.002). In ILAE, higher serum magnesium was suggestively associated with reduced risks of focal epilepsy (OR = 0.25, 95% CI 0.10–0.62, p = 0.003). However, the results cannot be repeated in sensitivity analyses. As for serum calcium, the results did not reach statistical significance with overall epilepsy (OR = 0.60, 95% CI, 0.31–1.17, p = 0.134). However, genetically predicted serum calcium concentrations showed an inverse association with risk of generalized epilepsy (OR = 0.35, 95% CI, 0.17–0.74, p = 0.006).ConclusionThe current MR analysis did not support a causal relationship between serum magnesium and epilepsy, but showed a causally negative association between genetically determined serum calcium and generalized epilepsy.

Identifying novel proteins for migraine by integrating proteomes from blood and CSF with genome‐wide association data

“…In recent years, with the availability of large genetic studies on various traits including plasma proteins and diseases, Mendelian randomization (MR) analysis has emerged as a powerful means for identifying causal links between traits and diseases, as well as between potential drug targets and diseases. 14 , 15 , 16 , 17 , 18 By leveraging genetic variants as instrumental variables, MR analysis can provide valuable insights into the causal effects of specific proteins on disease outcomes. 19 …”

“…Considering the emerging understanding of the role of plasma proteins and inflammatory factors in migraine, there is a compelling need to further investigate these associations using advanced analytical techniques. In recent years, with the availability of large genetic studies on various traits including plasma proteins and diseases, Mendelian randomization (MR) analysis has emerged as a powerful means for identifying causal links between traits and diseases, as well as between potential drug targets and diseases 14–18 . By leveraging genetic variants as instrumental variables, MR analysis can provide valuable insights into the causal effects of specific proteins on disease outcomes 19 …”